Medicament container

ABSTRACT

A medicament container ( 10 ) is disclosed which comprises at least two compartments ( 21, 22 ). Each of the compartments ( 21, 22 ) is adapted to contain a dose of a medicament in powdered form and is provided with at least one opening ( 23 ) through which, in use, the medicament can be dispensed. The container ( 10 ) is preferably cylindrical in form, the diameter of the cylinder being greater than its depth such that the container ( 10 ) has the form of a squat drum.

This application is a national stage application under 35 U.S.C. §371from PCT Application No. PCT/GB02/01728 filed Apr. 12, 2002, whichclaims the priority benefit of Great Britain Application No. 0109693.2filed Apr. 19, 2001 and Great Britain Application No. 0200063.6 filedJan. 3, 2002.

This invention relates to a medicament container, in particular to acontainer adapted to contain a plurality of unit doses of one or morepowdered solid medicaments intended for administration by inhalation,and to a method of administration of such medicaments from such acontainer.

The administration of medicaments by inhalation is well known. Suchmedicaments are often administered in the form of solid powders.Pressurised metered dose inhalers (MDI's) are one well-known form ofadministration, but concerns about the environmental effects of thepropellants used in such systems has lead to increased attention onso-called dry powder inhalers. In such inhalers, a dose of powderedmedicament is entrained in a swirling airflow and inhaled, the swirlingairflow normally being created by the act of inhalation.

One form of dry powder inhaler is described in International PatentApplication WO 98/26828. This device utilises medicament containershaving the form of squat drums which are held in a chamber and caused bythe patient's inspiratory airflow to undergo an epicyclic motion. Thecontainers have openings around their periphery through which themedicament is dispensed into the airflow and hence is inhaled by thepatient.

In the treatment of diseases of the airways, or indeed other diseasesthat are treated by inhalation therapy, it is not unusual for two ormore different medicaments to be prescribed. Most commonly, thisinvolves the patient in the separate administration of the two differentdrugs, either taking one straight after the other or taking the twomedicaments according to two different administration regimes. This canlead to errors, eg as a result of a patient administering to himself twodoses of one medicament, rather than one dose of each of twomedicaments. The resulting overdose of one drug, and underdose of theother, can seriously reduce the therapeutic benefit to the patient, orcan even be dangerous to the patient.

There have now been devised novel forms of medicament container that arespecifically adapted for the delivery of combinations of two (or more)different medicaments by inhalation.

According to the invention, there is provided a medicament containercomprising at least two compartments, each of said compartments beingadapted to contain a dose of a medicament in powdered form and eachcompartment being provided with at least one opening through which, inuse, said medicament can be dispensed.

The medicament container according to the invention is advantageousprimarily in that it permits the simultaneous administration of morethan one medicament and thereby reduces the risk of mis-administrationof two medicaments, in particular reducing the risk that the medicamentsmay be administered in the wrong ratios. Since the two medicaments aredispensed simultaneously, they are intimately mixed duringadministration and are therefore delivered to the target tissue, eg thepatient's lungs or nasal cavity, simultaneously and with equalefficiency.

The container according to the invention most preferably has a circularor substantially circular cross-section, the diameter of the circlebeing greater than the depth of the container. Such a shape isparticularly suitable for use in devices of the type disclosed in WO98/26828. Containers of such a form may be generally cylindrical inshape. At least one end of the cylindrical container is preferablysubstantially flat, such that in use the container may rest upon thatend. In such a case, the container has the form of a squat drum.However, one or both ends of the cylinder may be somewhat convex (orconcave). The shape may therefore be discus-like.

The compartments are most preferably disposed one above the other, alongthe longitudinal axis of a cylindrical or similar container. However,other arrangements may also be employed, eg a plurality of compartmentsarranged as segments of a cylindrical disc. The container may, forinstance; take the form of a squat cylindrical drum divided by adiametral wall into two hemicylindrical compartments.

The dispensing apertures are preferably formed around the periphery ofthe compartments. Most preferably, there are a plurality of suchapertures in each compartment, preferably equiangularly spaced aroundthe wall of the compartment.

The dispensing apertures may all be of equal size. Alternatively, thedispensing apertures in different compartments may be of differentsizes. This may lead to differences in the rate of delivery of themedicaments from the compartments into the airstream that is inhaled.For example, relatively large apertures in one compartment may lead tovery rapid emptying of a first medicament from that compartment, whilerelatively small apertures in another compartment may lead to slowerrelease of another medicament from that compartment.

When used in systems such as those disclosed in WO 98/26828, thecontainer is caused to undergo an epicyclic motion, in which it orbitswithin a swirl chamber and simultaneously rotates about its own axis.

The container is preferably manufactured from materials that areimpermeable or substantially impermeable to moisture.

The container most commonly comprises two compartments, adapted toreceive doses of two different medicaments. However, more than twocompartments may be present, and references herein to the use of thecontainer to administer two different medicaments should be understoodto encompass the possibility that more than two medicaments may beinvolved. It will also be apparent that more than one compartment may befilled with the same medicament. The container may therefore be used toadminister different total dosages of a single medicament, depending onthe number of compartments that are filled, or two or more medicamentsmay be filled separately into some or all of a larger number ofcompartments, thereby allowing some variation in the ratio of themedicaments that are administered. In another alternative, two or morecompartments may be charged with the same medicament, but formulateddifferently, eg for delivery to different regions of the target tissue.For instance, different compartments may contain a medicament in formshaving different particle size distributions.

Examples of combinations of medicaments that may be incorporated intoseparate compartments of a medicament container according to theinvention are:

Bronchodilators (β₂-agonists) and steroids, eg

-   -   formoterol and budesonide    -   salmeterol and fluticasone    -   formoterol and fluticasone    -   salmeterol and budesonide

Anticholinergics and steroids, eg

-   -   ipratropium bromide and budesonide    -   ipratropium bromide and fluticasone    -   oxitropium bromide and budesonide    -   oxitropium bromide and fluticasone

Non-steroidal anti-inflammatory drugs (NSAIDs) and steroids oranti-cholinergics, eg

-   -   sodium cromoglycate and budesonide    -   sodium cromoglycate and fluticasone    -   sodium cromoglycate and ipratropium bromide    -   sodium cromoglycate and oxitropium bromide    -   nedocromil sodium and budesonide    -   nedocromil sodium and fluticasone    -   nedocromil sodium and ipratropium bromide    -   nedocromil sodium and oxitropium bromide

Normal-acting and long-acting formulations of the same activeingredient, eg proteins and peptides, for instance insulin formulationsfor both fast and continued medication.

The container according to the invention is preferably supplied,pre-loaded with the medicaments that are to be administered, inpackaging which seals the dispensing apertures until the container isremoved from the packaging and introduced into the delivery device foruse. Suitable forms of such packaging may include variations on theforms of packaging disclosed in WO 98/26828. Alternatively, one or morecontainers according to the invention may be pre-loaded into amedicament delivery device, again as disclosed in WO 98/26828, thedevice being intended to be discarded after the last of the pre-loadedmedicament containers has been used.

The invention will now be described in greater detail, by way ofillustration only, with reference to the accompanying drawings, in which

FIG. 1 is a perspective view of a first embodiment of a medicamentcontainer according to the invention;

FIG. 2 is a sectional view of the container of FIG. 1;

FIG. 3 is an exploded, sectional view of a second embodiment of amedicament container according to the invention;

FIG. 4 is a plan view of a medicament inhaler device loaded with amedicament container according to the invention, showing the path ofmovement of the container during use; and

FIG. 5 is a sectional view of a third embodiment of a medicamentcontainer according to the invention.

Referring first to FIG. 1, a first embodiment of a medicament containeraccording to the invention is generally designated 10. The container 10has the form of a relatively squat cylinder with a diameter ofapproximately 10 mm and a height of approximately 6 mm.

The container 10 is assembled from three components, shown more clearlyin FIG. 2. These are an upper compartment shell 11, a lower compartmentshell 12 and a closure 13. All three components 11, 12, 13 are pressedfrom thin aluminium sheet. Alternatively, the components 11, 12, 13 maybe formed in plastics material, eg by injection moulding.

The components 11, 12, 13 are fitted together so as to define upper andlower medicament compartments 21,22, which are closed save fordispensing openings 23 that are provided at equiangularly spacedintervals in the wall of each of the compartments 21,22. The openings 23are disposed in planes approximately central to each of the respectivecompartments 21,22.

Each of the upper and lower compartment shells 11, 12 take the form ofopen-mouthed cylinders. The upper compartment shell 11 is formed nearits open base with an inwardly-projecting, annular rib 15 that engages acorresponding annular groove 16 formed near the top of the lowercompartment shell 12. Likewise, the lower compartment shell 12 has anannular rib 17 formed near its base that cooperates with a groove 18formed in an upstanding rim 19 around the periphery of the closure 13.

The container 10 is assembled by pressing the closed end of the lowercompartment shell 12 into the open mouth of the upper compartment shell11, such that the rib 15 engages in the groove 16. This closes the uppercompartment shell 11. Similarly, the closure 13 is pressed into the openmouth of the lower compartment 12 such that the rib 17 engages in thegroove 18, thereby closing the lower compartment shell 12.

In practice, the assembly process described above would also include thesteps of filling a dose of medicament into each compartment. This may befacilitated by assembling the container 10 in an inverted condition. Adose of a first medicament is filled into the upper compartment shell11, which is then closed by application of the lower compartment shell12. A dose of a second medicament is then filled into the lowercompartment shell 12, which is then closed by application of the closure13.

It will generally be desirable for the openings 23 to be closed duringthe filling and assembly process. To achieve this, the assembly processmay be carried out by fitting the components sequentially into a packagein which the container is to be supplied, and which incorporatesappropriate seals for the openings 23.

FIG. 3 is an exploded, cross-sectional view of a second embodiment of amedicament container according to the invention, generally designated110. This comprises three components, all of which are injection mouldedin rigid, moisture-impermeable plastics material. The three componentsare a main body 111 and two identical closure caps 112, 113. The mainbody 111 is in the form of a cylinder which is open at both ends but hasa central partition 114 that divides the body 111 into two compartments121, 122. The dimensions of the body 111 are similar to the overalldimensions of the embodiment of FIGS. 1 and 2.

The open ends of the body 111 are closed by the respective closure caps112, 113, each of which engages over the respective end of the body 111with a tight interference fit.

As for the first embodiment, each compartment 121, 122 of the embodimentof FIG. 3 is formed with dispensing openings 123.

FIG. 4 shows an inhaler device of the type disclosed in WO 98/26828. Forthe purposes of the present application, it is sufficient to note thatthe inhaler (generally designated 201) includes a swirl chamber 202which is circular in form. A pillar 203 is present in the centre of thechamber 202.

The inhaler 201 has a mouthpiece 204 at which a patient can inhale. Suchinhalation causes air to be drawn into the chamber 202 via air inlets205. The arrangement of these inlets 205 is such that the air flowwithin the chamber 202 is generally tangential. The effect of this airflow within the chamber 202 is to cause a medicament container 206similar to either of the two embodiments described above to rotatearound the chamber 202, as indicated by the larger curved arrow in FIG.4. In undergoing this motion, the container 206 “hugs” the wall of thechamber 202. At the same time, the container 206 rotates about its ownaxis, as indicated by the smaller curved arrow. The container 206 thusundergoes an epicyclic motion, constrained by the wall of the chamber202 while simultaneously spinning about its own axis.

As indicated by the short arrows in FIG. 4, medicament powder isdispensed from the container 206, under the influence of centrifugalforces, via the dispensing openings (not visible in FIG. 4) and insubstantially all directions. Medicament powder is dispensedsimultaneously from both compartments in the container 206, the twomedicaments becoming entrained and intimately mixed in the swirlingairflow inhaled by the patient.

Finally, FIG. 5 shows a third embodiment of a medicament container 301according to the invention. This comprises three interfitting components302, 303, 304, each of which is injection-moulded in plastics material.The lowermost (as viewed in FIG. 5) component 302 has the form of ashallow, flat-bottomed bowl, having an upstanding rim 305 which has anexternally-extending peripheral lip 306. The intermediate component 303is formed with a downwardly-depending skirt 307 that engages over thelip 306 with a snap fit. The upper part of the intermediate component303 is formed as a shallow bowl, similar in form to that defined by thelowermost component 302, again having an upstanding rim 308 with a lip309. The topmost component 304 is domed, with a peripheral skirt 310that engages with a snap fit over the rim 308 and lip 309 of theintermediate component.

The lowermost component 302 and the intermediate component 303 betweenthem define a first chamber 311, and the intermediate component 303 andthe topmost component 304 define a second chamber 312. Series ofopenings 313,314 (only some of which are shown in FIG. 5) are formedrespectively in the intermediate component 303 and the topmost component304 to permit, in use, egress of medicament from the respective chambers311,312.

It will be noted that the internal lower surfaces of the chambers311,312 are curved. This arrangement serves to guide medicament withinthe chambers 311,312 towards the respective openings 313,314 under theinfluence of centrifugal forces, and hence facilitates dispensing ofmedicament from the chambers 311,312.

1. A medicament container comprising at least two compartments, each ofsaid compartments being adapted to contain a dose of a medicament inpowdered form and each compartment being provided with at least oneopening through which, in use, said medicament can be dispensed, themedicament container being arranged to allow doses of medicamentcontained in two or more compartments to be dispensed simultaneouslywherein a user inhaling though a delivery device causes rotation of thecontainer about an axis to dispense the medicament though the opening,wherein the container has a circular or substantially circularcross-section, and the container is pre-loaded with the doses ofmedicament, in a packaging which seals the openings until the medicamentcontainer is removed from the packaging and introduced into the deliverydevice for use.
 2. A medicament container according to claim 1, whereinthe diameter of the circular or substantially circular cross-section isgreater than the depth of the container.
 3. A medicament containeraccording to claim 1, wherein the container is generally cylindrical inshape.
 4. A medicament container according to claim 3, wherein one orboth ends of the cylinder are convex or concave.
 5. A medicamentcontainer according to claim 4, wherein at least one end of thecontainer is substantially fiat.
 6. A medicament container according toclaim 3, wherein the compartments are disposed one above the other,along a longitudinal axis of the container.
 7. A medicament containeraccording to claim 1, wherein the container comprises a plurality ofcompartments arranged as segments of a cylindrical disc.
 8. A medicamentcontainer according to claim 7, wherein the container takes the form ofa cylindrical drum divided by a diametral wall into two hemicylindricalcompartments.
 9. A medicament container according to claim 1, whereinthe dispensing apertures are formed around the periphery of thecompartments.
 10. A medicament container according to claim 1, whereineach compartment has a plurality of apertures.
 11. A medicamentcontainer according to claim 10 wherein the apertures of eachcompartment are equiangularly spaced around the wall of the compartment.12. A medicament container according to claim 1, wherein the dispensingapertures are all of equal size.
 13. A medicament container according toclaim 1, wherein the dispensing apertures in different compartments areof different sizes.
 14. A medicament container according to claim 1,wherein the container is manufactured from materials that areimpermeable or substantially impermeable to moisture.
 15. A medicamentcontainer according to claim 1, wherein the container comprises twocompartments.
 16. A medicament container according to claim 1, whereinmore than one compartment contains the same medicament.
 17. A medicamentcontainer according to claim 16, wherein two or more compartmentscontain the same medicament, but formulated differently.
 18. Amedicament container according to claim 17, wherein two or morecompartments contain the same medicament, but having different particlesize distributions.
 19. A medicament container according to claim 1,wherein the container contains a combination of medicaments incorporatedinto separate compartments.
 20. A medicament container according toclaim 19, wherein the combination of medicaments comprises abronchodilator (β₂-agonist) and a steroid.
 21. A medicament containeraccording to claim 20, wherein the combination of bronchodilator(β₂-agonist) and steroid is selected from the group consisting of:formoterol and budesonide; salmeterol and fluticasone; formoterol andfluticasone; and salmeterol and budesonide.
 22. A medicament containeraccording to claim 21, wherein the combination of anticholinergic andsteroid is selected from the group consisting of: ipratropium bromideand budesonide; ipratropium bromide and fluticasone; oxitropium bromideand budesonide; and oxitropium bromide and fluticasone.
 23. A medicamentcontainer according to claim 19, wherein the combination of medicamentscomprises an anticholinergic and a steroid.
 24. A medicament containeraccording to claim 19, wherein the combination of medicaments comprisesan anti-inflammatory drug (NSAID) and a steroid or an anti-cholinergic.25. A medicament container according to claim 24, wherein thecombination of anti-inflammatory drug (NSAID) and steroid oranti-cholinergic is selected from the group consisting of: sodiumcromoglycate and budesonide; sodium cromoglycate and fluticasone; sodiumcromoglycate and ipratropium bromide; sodium cromoglycate and oxitropiumbromide; nedocromil sodium and budesonide; nedocromil sodium andfluticasone: nedocromil sodium and ipratropium bromide; and nedocromilsodium and oxitropium bromide.
 26. A medicament container according toclaim 19, wherein the combination of medicaments comprises anormal-acting and a long-acting formulation of the same activeingredient.
 27. A medicament container according to claim 26, whereinthe active ingredient is selected from the group consisting of proteinsand peptides.
 28. A medicament container according to claim 27, whereinthe active ingredient is an insulin formulation.
 29. A medicamentcontainer comprising at least two compartments, each of the compartmentsadapted to contain a dose of a medicament in powdered form and eachcompartment being provided with at least one opening through which, inuse, the medicament can be dispensed, the medicament container beingarranged to allow doses of medicament contained in two or morecompartments to be dispensed simultaneously wherein a user inhalingthough a delivery device causes rotation of the container about an axisto dispense the medicament though the opening, wherein the container ispre-loaded with the doses of medicament in a packaging which seals theopenings until the medicament container is removed from the packagingand introduced into the delivery device for use.